title: Cascade testing of primary care blood samples with hyperferritinaemia identifies subjects with iron overload and porphyria cutanea tarda.
abstract: BACKGROUND
  Serum ferritin is routinely used as a first line test for iron status. Testing subjects with low pre-test probability often results in unexpected abnormal results. Raised ferritin is typically found in subjects with iron overload, liver disease, malignancy or inflammation. We sought to determine whether primary care patients with high ferritin had either porphyria cutanea tarda (PCT) or hereditary haemochromatosis (HH).
  
  
  METHODS
  Redundant serum samples were collected from consecutive specimens with high ferritin (>500 µg/L) which had been received from primary care sources. Samples were analysed for serum iron and iron-binding capacity and for porphyrins by fluorescence scanning and HPLC.
  
  
  RESULTS
  There were 240 samples (91 females, 149 males) which represented 2.7% of total over the collection period. Serum iron was 17.3 (18.9) µmol/L (median (IQR)), TIBC 47.3 (14.2) µmol/L and transferrin saturation 35.7 (41.1) %. There were 87/240 (36%) with transferrin saturation >45% (57 males, 30 females). Of the samples 19/236 (8%) were positive for porphyrins by spectrofluorimetry and 14/15 (4 insufficient sample) had total porphyrins >11.2 nmol/L (40(63) median (IQR)) with 3/15 (1.25%) having a typical pattern for PCT.
  
  
  CONCLUSIONS
  This study demonstrates the feasibility of cascading tests using laboratory protocols and confirms the ability to identify potential cases. However, further studies for HH genotype and urine and stool porphyrin analysis will be necessary to confirm the diagnoses.
authors.affiliation: Blood Sciences, Leeds General Infirmary, Leeds, UK.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Baddams
authors.affiliation: Blood Sciences, Leeds General Infirmary, Leeds, UK.
authors.forename: Tim
authors.initials: T
authors.lastname: Degg
authors.affiliation: Blood Sciences, Leeds General Infirmary, Leeds, UK Julian.barth@leedsth.nhs.uk.
authors.forename: Julian H
authors.initials: JH
authors.lastname: Barth
mesh_terms: D001774:Blood Chemical Analysis / Q000295:instrumentation / Q000379:methods / Q000592:standards; D005260:Female; D006432:Hemochromatosis / Q000097:blood* / Q000175:diagnosis; D006801:Humans; D007501:Iron / Q000097:blood*; D008297:Male; D017119:Porphyria Cutanea Tarda / Q000097:blood* / Q000175:diagnosis; D011166:Porphyrins / Q000097:blood*; D014168:Transferrin / Q000378:metabolism*
chemical_list: D011166:Porphyrins; D014168:Transferrin; D007501:Iron
keywords: Inborn errors of metabolism; haemoglobin disorders; iron disorders